Improving Vaccination for Young Children (IVY): A Stepped-Wedge Cluster Randomized Trial.

BACKGROUND: High childhood vaccination rates are critical for public health. We hypothesized that implementation of a vaccine education and quality improvement (QI) program, Improving Vaccinations for Young Children (IVY), would improve childhood vaccine rates. METHODS: Eight pediatric practices (3 academic-based, 5 community-based) were randomized to implement IVY within a stepped-wedge cluster randomized trial (SWCRT) in middle Tennessee. Two educational modules on vaccines were developed using best practices in instructional design. Modules were provided electronically and were tailored to providers or office staff. Practices completed in-person QI coaching sessions and selected at least 2 vaccination-related QI changes. Data were collected monthly. The primary analysis examined intervention effect on the primary outcome of Combination 10 vaccination status for children who turned 2 in the previous month. Combination 10 status without influenza vaccine was a secondary outcome, and exploratory analyses assessed intervention effects after adjusting for time and practice type. RESULTS: Data from 4041 patients (1788 control; 2253 intervention) were collected. The intervention effect was not significant on the primary outcome (OR = 1.01; 95% CI [0.76, 1.34]; P > .9), however there were positive intervention effects in secondary and exploratory models analyzing Combination10 rates without flu, including models adjusting for variation over time (0.20; 95% CI [0.04,0.35]; P = .01) and practice type (higher vaccination rate in academic practices, 0.23; 95% CI [0.03,0.42]; P = .03). CONCLUSIONS: Combination 10 rates were not significantly improved with IVY, yet evidence of beneficial effect on rates without flu vaccine was found. Future studies could evaluate effects over a longer time period and within a larger practice sample.

Formal training in vaccine safety to address parental concerns not routinely conducted in U.S. pediatric residency programs.

OBJECTIVE: To determine if U.S. pediatric residency programs provide formal training in vaccine safety to address parental vaccine concerns. METHODS: An electronic survey was mailed to all members of the Association of Pediatric Program Directors (APPD) to assess (1) if U.S. pediatric residency programs were providing formal vaccine safety training, (2) the content and format of the training if provided, and (3) interest in a training module for programs without training. Two follow-up surveys were mailed at 2 week intervals. Responses to the survey were collected at 4 weeks following the last mailing and analyzed. Logistic regression was used to assess the impact of program size on the likelihood of vaccine safety training. Pearson's chi square was used to compare programs with and without formal vaccine safety training in 5 U.S. regions. RESULTS: The survey was sent to 199 APPD members; 92 completed the survey (response rate 46.2%). Thirty-eight respondents (41%) had formal training in vaccine safety for pediatric residents at their programs; 54 (59%) did not. Of those that did not, the majority (81.5%) were interested in formal vaccine safety training for their residents. Of all respondents, 78% agreed that training in vaccine safety was a high priority for resident education. Thirty-five percent of all respondents agreed that local parental attitudes about vaccines influenced the likelihood of formal vaccine safety training. CONCLUSION: Most pediatric residency programs surveyed do not include formal training on vaccine safety; yet, such training is supported by pediatric residency program directors as a priority for pediatric residents.

Live vaccine use and safety in DiGeorge syndrome.

OBJECTIVE: Live vaccines are generally contraindicated in patients with DiGeorge syndrome (DGS), a congenital disorder characterized by cellular immune deficiency. Vaccine utilization and safety in this population are not well described. This study examined vaccination patterns and adverse events following live immunization (AEFLI) in these individuals. METHODS: A multicenter retrospective cohort study was conducted in subjects with DGS confirmed by fluorescence in situ hybridization assay (chromosome 22q11.2 microdeletion). Live vaccine-preventable illnesses, vaccination coverage and timeliness, and AEFLIs in the 56-day window after live vaccination were examined. Bivariate and multivariable analyses assessed the impact of demographics medical history, timing of diagnostic confirmation, and preceding immune function on vaccination patterns and AEFLIs. RESULTS: Of 194 subjects, 77% and 75% received measles-mumps-rubella (MMR) and varicella vaccines, respectively; 58% completed recommended vaccinations by age 19 to 35 months. Adverse events occurred after 14% and 20% of MMR and varicella vaccine doses, respectively. Most events were minor, few were serious, and no deaths were reported in post-live vaccination windows. Although early diagnostic confirmation negatively affected live vaccination coverage and timeliness (P < .001), baseline CD4% did not differ between subjects who did or did not receive live vaccines by 12 to 18 months. Among varicella vaccine recipients, those with a subsequent adverse event had a lower preceding CD4% (24.8% ± 7.3%) than those without (35.5% ± 11.7%) (P < .05); no CD4% differences were observed with MMR vaccination. Fourteen unvaccinated subjects experienced live vaccine-preventable illnesses. CONCLUSIONS: Live vaccines were frequently given and generally well-tolerated among patients with DGS with mild-to-moderate immunosuppression.

Evaluation of the feasibility of a state-based vaccine safety advice network.

The vaccine safety advice network is a collaborative pilot project between Vanderbilt University Medical Center, the Tennessee Department of Health, and the Centers for Disease Control and Prevention to assess the feasibility of addressing vaccine safety questions posed by healthcare providers in near real-time. Using a two-tier response system and an electronic database for query submission, the pilot project received ten queries in three and one half months. Two of three pre-specified benchmarks for program evaluation, addressing queries within 24 h of receipt and 100% provider satisfaction, were met; one benchmark, the percentage of questions addressed by Tier 1 staff, was not met. Limitations included few submitted queries primarily involving children in the pilot period, "after-only" program evaluation, and limited geographic generalizability. The study demonstrates a successful partnership between federal, state and academic institutions and a feasible method to respond to healthcare provider inquiries about vaccine safety in near real-time.

A systematic review of validated methods to capture several rare conditions using administrative or claims data.

PURPOSE: To identify and assess billing, procedural, or diagnosis code, or pharmacy claim-based algorithms used to identify the following health outcomes in administrative and claims databases: acute disseminated encephalomyelitis (ADEM), optic neuritis, tics, and Henoch Schönlein purpura (HSP). METHODS: We searched the MEDLINE database from 1991 to September 2012 using controlled vocabulary and key terms related to the conditions. We also searched the reference lists of included studies. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria and extracted case validation data from those studies meeting inclusion criteria. RESULTS: Two eligible studies addressed ADEM, two addressed optic neuritis, and four studies addressed tics. Only one study addressed HSP. Among these, one study of ADEM reported a positive predictive value of 66%, however the identification algorithm contained a combination of International Classification of Diseases (ICD) codes and other identification methods and the performance of the ICD-9 codes alone was not reported. No other studies reported validation data. CONCLUSIONS: The lack of data on the validity of algorithms to identify these conditions may hamper our ability to determine incidence patterns with respect to infection and vaccination exposures. Further epidemiologic research to define validated methods of identifying cases could improve surveillance using large linked healthcare databases.

A systematic review of validated methods for identifying transverse myelitis using administrative or claims data.

PURPOSE: To identify and assess billing, procedural, or diagnostic code algorithms used to identify transverse myelitis in administrative databases. METHODS: We searched the MEDLINE database from 1991 to September 2012 using controlled vocabulary and key terms related to transverse myelitis. We also searched the reference lists of included studies. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria. Two reviewers independently extracted data regarding participant and algorithm characteristics. RESULTS: Three studies met criteria for inclusion in this review. The only algorithm based solely on administrative claims data with a reported positive predictive value included five ICD-9 codes (codes 341.20, 341.21, 341.22, 323.8, 323.9). The positive predictive value for physician-diagnosed acute transverse myelitis was 62%. CONCLUSIONS: More research is needed to establish an accurate algorithm to identify transverse myelitis in large administrative databases using diagnosis and/or procedure codes. Use of standardized consensus definitions, clear description for algorithm selection, and reporting of validation procedure and results would be most beneficial.

A systematic review of validated methods for identifying uveitis using administrative or claims data.

PURPOSE: To review algorithms used to identify uveitis in administrative and claims databases. METHODS: We searched the MEDLINE database via PubMed from 1991 to September 2012 using vocabulary and key terms related to uveitis. We also searched the reference lists of included studies. Two investigators independently assessed studies against pre-determined inclusion criteria. The same two investigators independently extracted data regarding participant and algorithm characteristics and assessed a study's methodological rigor using a pre-defined approach. RESULTS: Seven studies met inclusion criteria. Variability exists among algorithms employed in these studies for finding cases of uveitis and related conditions as well as in use and implementation of validation methods. Of the seven included studies, three involved case validation. One used a narrow algorithm in addition to text mining of electronic medical records to identify incident cases and found a positive predictive value of 52.1%. The other two, which used broader uveitis definitions and included both incident and prevalent cases, found positive predictive values of 24.8% and 52.6%. CONCLUSIONS: Further research, with case as well as individual code validation, is needed to determine appropriate uveitis algorithms for purposes of active surveillance in administrative data. Decisions about which algorithm to use will depend on the desired balance of sensitivity and specificity.

A randomized trial to increase acceptance of childhood vaccines by vaccine-hesitant parents: a pilot study.

OBJECTIVE: A cluster randomized trial was performed to evaluate an educational intervention to improve parental attitudes and vaccine uptake in vaccine-hesitant parents. METHODS: Two primary care sites were randomized to provide families with either usual care or an intervention (video and written information) for vaccine-hesitant parents. Eligible parents included those presenting for their child's 2-week well-child visit with performance on the Parent Attitudes about Childhood Vaccines (PACV) survey suggesting vaccine hesitancy (score ≥25). Enrollees completed PACV surveys at the 2-month well-child visit and vaccination status at 12 weeks of age was assessed. The primary outcome was the difference in PACV scores obtained at enrollment and 2 months between the 2 groups. The proportion of on-time vaccination was also compared at 12 weeks. RESULTS: A total of 454 parents were approached, and 369 (81.3%) participated; 132 had PACV scores of ≥25 and were enrolled, 67 in the control group (mean PACV score 37) and 55 in the intervention group (mean PACV score 40). Two-month PACV surveys were completed by 108 (∼90%) of enrollees. Parents in the intervention group had a significant decrease in PACV score at 2 months compared to control (median difference 6.7, P = .049); this remained significant after adjustment for baseline PACV score, race/ethnicity, and income (P = .044). There was no difference in the on-time receipt of vaccines between groups at 12 weeks. CONCLUSIONS: A brief educational intervention for vaccine-hesitant parents was associated with a modest but significant increase in measured parental attitudes toward vaccines.

Clinical assessment of serious adverse events in children receiving 2009 H1N1 vaccination.

BACKGROUND: Monovalent 2009 H1N1 influenza vaccines were licensed and administered in the United States during the H1N1 influenza pandemic between 2009 and 2013. METHODS: Vaccine Adverse Event Reporting System received reports of adverse events following immunization (AEFI) after H1N1 vaccination. Selected reports were referred to the Centers for Disease Control and Prevention's Clinical Immunization Safety Assessment network for additional review. We assessed causality using modified World Health Organization criteria. RESULTS: There were 3,928 reports of AEFI in children younger than age 18 years after 2009 H1N1 vaccination received by January 31, 2010. Of these, 214 (5.4%) were classified as serious nonfatal and 109 were referred to Clinical Immunization Safety Assessment for further evaluation. Ninety-nine (91%) had sufficient initial information to begin investigation and are described here. The mean age was 8 years (range, 6 months-17 years) and 38% were female. Median number of days between vaccination and symptom onset was 2 (range, -11 days to +41 days). Receipt of inactivated, live attenuated, or unknown type of 2009 H1N1 vaccines was reported by 68, 26 and 5 cases, respectively. Serious AEFI were categorized as neurologic events in 47 cases, as hypersensitivity in 15 cases and as respiratory events in 10 cases. At the time of evaluation, recovery was described as complete (61), partial (16), no improvement (1), or unknown (21). Causality assessment yielded the following likelihood of association with 2009 H1N1 vaccination: 8 definitely; 8 probably; 21 possibly; 43 unlikely; 17 unrelated; and 2 unclassifiable. CONCLUSIONS: Most AEFI in children evaluated were not causally related to vaccine and resolved without sequelae. Detailed clinical assessment of individual serious AEFI can provide reassurance of vaccine safety.

Causality assessment of serious neurologic adverse events following 2009 H1N1 vaccination.

BACKGROUND: Adverse events occurring after vaccination are routinely reported to the Vaccine Adverse Event Reporting System (VAERS). We studied serious adverse events (SAEs) of a neurologic nature reported after receipt of influenza A (H1N1) 2009 monovalent vaccine during the 2009-2010 influenza season. Investigators in the Clinical Immunization Safety Assessment (CISA) network sought to characterize these SAEs and to assess their possible causal relationship to vaccination. METHODS: Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) physicians reviewed all SAE reports (as defined by the Code of Federal Regulations, 21CFR§314.80) after receipt of H1N1 vaccine reported to VAERS between October 1, 2009 and March 31, 2010. Non-fatal SAE reports with neurologic presentation were referred to CISA investigators, who requested and reviewed additional medical records and clinical information as available. CISA investigators assessed the causal relationship between vaccination and the event using modified WHO criteria as defined. RESULTS: 212 VAERS reports of non-fatal serious neurological events were referred for CISA review. Case reports were equally distributed by gender (50.9% female) with an age range of 6 months to 83 years (median 38 years). The most frequent diagnoses reviewed were: Guillain-Barré Syndrome (37.3%), seizures (10.8%), cranial neuropathy (5.7%), and acute disseminated encephalomyelitis (3.8%). Causality assessment resulted in classification of 72 events as "possibly" related (33%), 108 as "unlikely" related (51%), and 20 as "unrelated" (9%) to H1N1 vaccination; none were classified as "probable" or "definite" and 12 were unclassifiable (6%). CONCLUSION: The absence of a specific test to indicate whether a vaccine component contributes to the pathogenesis of an event occurring within a biologically plausible time period makes assessing causality difficult. The development of standardized protocols for providers to use in evaluation of adverse events following immunization, and rapid identification and follow-up of VAERS reports could improve causality assessment.

Overview of the Clinical Consult Case Review of adverse events following immunization: Clinical Immunization Safety Assessment (CISA) network 2004-2009.

BACKGROUND: In 2004 the Clinical Consult Case Review (CCCR) working group was formed within the CDC-funded Clinical Immunization Safety Assessment (CISA) Network to review individual cases of adverse events following immunizations (AEFI). METHODS: Cases were referred by practitioners, health departments, or CDC employees. Vaccine Adverse Event Reporting System (VAERS) searches and literature reviews for similar cases were performed prior to review. After CCCR discussion, AEFI were assessed for a causal relationship with vaccination and recommendations regarding future immunizations were relayed back to the referring physicians. In 2010, surveys were sent to referring physicians to determine the utility and effectiveness of the CCCR service. RESULTS: CISA investigators reviewed 76 cases during 68 conference calls between April 2004 and December 2009. Almost half of the cases (35/76) were neurological in nature. Similar AEFI for the specific vaccines received were discovered for 63 cases through VAERS searches and for 38 cases through PubMed searches. Causality assessment using the modified WHO criteria resulted in classifying 3 cases as definitely related to vaccine administration, 12 as probably related, 16 as possibly related, 18 as unlikely related, 10 as unrelated, and 17 had insufficient information to assign causality. The physician satisfaction survey was returned by 30 (57.7%) of those surveyed and a majority of respondents (93.3%) felt that the CCCR service was useful. CONCLUSIONS: The CCCR provides advice about AEFI to practitioners, assigns potential causality, and contributes to an improved understanding of adverse health events following immunizations.